Method and system for adjusting a neurostimulation therapy

ABSTRACT

The systems and methods described herein generally relate to adjusting a neurostimulation (NS) therapy based on drug pharmacokinetics of a patient. The systems and methods deliver an NS therapy to a portion of electrodes of a lead positioned proximate to neural tissue of interest, which is associated with a target region. The NS therapy is defined by stimulation parameters. The systems and methods determine a trigger event indicative of a drug being administered to a patient. The drug is configured to affect at least one of the neural tissue of interest or the target region. The systems and methods adjust one or more of the stimulation parameters based on the PS profile.

REFERENCE TO RELATED APPLICATIONS

The present application is a continuation application of, and claimspriority to, U.S. application Ser. No. 15/806,690, Titled “METHOD ANDSYSTEM FOR ADJUSTING A NEUROSTIMULATION THERAPY” which was filed on 8Nov. 2017, the complete subject matter of which is expresslyincorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

Embodiments herein generally relate to neurostimulation (NS) therapy andmore particularly to adjusting the NS therapy based on drugpharmacokinetics of a patient.

Conventional NS systems are devices that generate electrical pulses anddeliver the pulses to neural tissue to treat a variety of disorders. NSsystems may be used to manage one or more conditions of a patient bydelivering NS therapy. The NS systems can include deep brainstimulation, tremors, dystonia, spinal cord stimulation, dorsal rootganglion stimulation, peripheral nerve stimulation, and/or the like. TheNS therapy is delivered by the NS system as electrical impulses throughelectrodes implanted in the one or more target regions of the nervoussystem. The electrical impulses are configured by a clinician based onone or more stimulation parameters (e.g., an intensity, a frequency, apulse width, a duty cycle, an NS therapy type). The one or morestimulation parameters of the electrical impulses are static over time.

Concurrently with the static NS therapy, patients can manage thedisorder using drugs. The drugs can affect the therapeutic effectivenessof the NS therapy over time. For example, the drugs can causefluctuations of the NS therapy, such as not providing appropriate reliefand/or above what is tolerable to the patient (e.g., dyskinesia inParkinson Disease).neural tissue

A need remains for improved methods and systems for adjusting NStherapy.

SUMMARY

In accordance with an embodiment, a neurostimulation (NS) system isprovided. The system includes a lead having an array of electrodespositioned within a patient, and a memory having apharmacokinetic-stimulation (PS) profile related to a drug. The systemincludes a controller circuit configured to respond to instructionsstored on a non-transient computer-readable medium. The controllercircuit is configured to deliver an NS therapy to a portion of theelectrodes proximate to neural tissue of interest that is associatedwith a target region. The NS therapy is defined by stimulationparameters. The controller circuit is configured to determine a triggerevent indicative of a drug being administered to the patient. The drugis configured to affect at least one of the neural tissue of interest orthe target region. The controller circuit is configured to adjust one ormore of the stimulation parameters based on the PS profile.

In accordance with an embodiment, a method is provided for adjusting aneurostimulation (NS) therapy. The method includes delivering an NStherapy to a portion of electrodes of a lead positioned proximate toneural tissue of interest, which is associated with a target region. TheNS therapy is defined by stimulation parameters. The method includesdetermining a trigger event indicative of a drug being administered to apatient. The drug is configured to affect at least one of the neuraltissue of interest or the target region. The method includes adjustingone or more of the stimulation parameters based on the PS profile.

In accordance with an embodiment, a method is provided for adjusting aneurostimulation (NS) therapy. The method includes calculating anabsorption curve of a drug over time. The absorption curve is based on apharmacokinective characteristic of the drug. The method includesdetermining a response curve of a patient based on a patient profile.The patient profile represents one or more physiological characteristicsof a patient. The method includes calculating a drug efficacy modelbased on the absorption curve and the response curve. The methodincludes defining a pharmacokinetic-stimulation (PS) profile based onthe drug efficacy model, and transmitting the PS profile to an NSsystem.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a schematic block diagram of an embodiment of aneurostimulation system.

FIGS. 2A-2I respectively depict stimulation portions of embodiments forinclusion at the distal end of a lead.

FIG. 3 illustrates a schematic block diagram of an embodiment of anexternal device.

FIG. 4 illustrates a flowchart of an embodiment of a method foradjusting a neurostimulation therapy.

FIG. 5 illustrates a graphical representation of an embodiment of anabsorption curve.

FIG. 6 illustrates a graphical representation of an embodiment of aresponse curve.

FIG. 7 illustrates a graphical representation of an embodiment of a drugefficacy model.

FIGS. 8-11 illustrate graphical representations of embodiments of apharmacokinetic-stimulation profile and the drug efficacy model shown inFIG. 7.

DETAILED DESCRIPTION

While multiple embodiments are described, still other embodiments of thedescribed subject matter will become apparent to those skilled in theart from the following detailed description and drawings, which show anddescribe illustrative embodiments of disclosed inventive subject matter.As will be realized, the inventive subject matter is capable ofmodifications in various aspects, all without departing from the spiritand scope of the described subject matter. Accordingly, the drawings anddetailed description are to be regarded as illustrative in nature andnot restrictive.

Embodiments herein describe a neurostimulation (NS) system configured todeliver NS therapy to a target region within a patient. The NS therapyis defined by one or more stimulation parameters. The stimulationparameters define the electrical characteristics (e.g., a frequency, anamplitude, a pulse width, an amplitude, a stimulation pattern, a dutycycle, an NS therapy type) of the NS therapy. The NS therapy isdelivered proximate to neural tissue of interest that is associated witha target region.

The NS system is configured to adjust the NS therapy when a triggerevent is detected. The trigger event corresponds to when a drug isadministered to the patient. The trigger event may be received by the NSsystem from an external device, such as a cell phone, laptop, computer,tablet, Near Field Communication (NFC) tag, Radio FrequencyIdentification (RFID) tag, drug retention device, and/or the like.Optionally, the trigger event may be based on a schedule stored in amemory of the NS system.

The NS system is configured to adjust the NS therapy (e.g., the one ormore stimulation parameters) based on a pharmacokinetic-stimulation (PS)profile. The PS profile is based on a drug efficacy model. The drugefficacy model represents an effectiveness of the drug on the patient.For example, the drug efficacy model includes a range of valuescorresponding to the physiological effect of the drug on the patientover time. The drug efficacy model is based on an absorption curve ofthe drug over time, a pharmacokinetic characteristic of the drug, and aresponse curve of the patient.

Terms

An “absorption curve” refers to a concentration of the drug in bloodplasma of the patient over time. Optionally, the absorption curve can beprovided by a manufacturer of the drug, regulatory agency, and/or thelike. The absorption curve may extend from when the drug is administeredto the patient (e.g., the trigger event) to when the concentration ofthe drug is negligible and/or zero. The absorption curve is based on thechemical characteristics of the drug, a dosage of the drug, a method onhow the drug is administered, and/or the like. The methods foradministering the drug may include orally (e.g., capsule, pill, liquid,tablet), suppository, syringe, inhalation into the lungs, injectionwithin the blood stream, and/or the like. The absorption curve can bederived from the pharmacokinetic characteristics of the drug. Thepharmacokinetic characteristics includes a predictive model (e.g.,liberation) of a rate of dissolution of the drug, a rate of movement ofthe drug into the bloodstream (e.g., absorption), and/or a rate ofdistribution of the drug in fluids and/or tissue of the patient from asite of the administration of the drug.

A “response curve” refers to a physiological response of the patientbased on a concentration of the drug. The response curve is based onphysiological characteristics of the patient, the dosage of the drug,the method for how the drug is administered, and/or the like. Thephysiological characteristics can include weight, age, height, and/orthe like. The response curve includes a rate that varies based on howthe concentration of the drug effects a physiology of the patient. Thephysiologic effect may include interruption and/or adjustment ofimpulses produced or received by neural tissue within the patient.

A “drug efficacy model” refers to a magnitude of physiological effectson the patient from the drug over time. The magnitude of physiologicaleffects represents the effect of the drug on the patient. The drugefficacy model can be derived from the response curve and the absorptioncurve. Optionally, the drug efficacy model can be generated based on theabsorption curve and a generalized response curve based on thephysiological characteristics of the patient.

An “NS therapy profile” is defined by sets of stimulation parameters forthe NS therapy. The NS therapy profile organizes the sets of thestimulation parameters in connection with a time period elapsed since atrigger event based on the drug efficacy model. For example, thestimulation parameters are organized such that select stimulationparameters are utilized for the NS therapy based on the magnitude ofphysiological effect of the drug efficacy model. Additionally oralternatively, the NS therapy profile may refer to a range ofstimulation parameters and weighted factors. The weighted factors shiftthe stimulation parameters of the NS therapy within the range based onthe drug efficacy model. For example, the NS therapy profile may haveselect weighted factors corresponding to the magnitude of physiologicaleffect provided by the drug efficacy model.

A “PS profile” is defined by stimulation parameters that vary for the NStherapy in relation to a patient over time based on the trigger event.The PS profile may include the NS therapy profile and/or the drugefficacy model. Optionally, the PS profile may include temporalinformation representing a drug schedule of the patient.

A “trigger event” refers an event indicating that the drug is beingadministered to the patient. The trigger event may be communicated tothe NS system from an external device. The external device can beoperated by a clinician (e.g., nurse, doctor) and/or the patient.Additionally or alternatively, the trigger event may be based on thedrug schedule. The drug schedule may represent points in time when thepatient is administered the drug. Additionally or alternatively, thetrigger event may be communicated to the NS system from a drug retentiondevice.

“Stimulation parameters” refer to electrical characteristics of the NStherapy. The stimulation parameters may represent a pulse width, afrequency, an amplitude, a duty cycle, an NS therapy type, and/or thelike. The NS therapy type can represent a characteristic of the NStherapy delivered by the NS system. The characteristic may correspond tostimulation and/or pulse patterns of the NS therapy. The pulse patternsmay be a burst stimulation waveform or a tonic stimulation waveform ofthe NS therapy. The tonic stimulation waveform represents a pulserepeated at a rate defined by the duty cycle. The burst stimulationwaveform represents a series of pulses grouped to form a pulse train.The pulse train may be repeated at a cycle rate defined by the dutycycle.

A “drug” refers to a chemical composition that is configured tointerrupt and/or adjust impulses produced or received by neural tissuewithin the patient. For example, the drug may include levodopa, adopamine agonist, safinamide, selegiline, rasagiline, amantadine,acetylcholinesterase inhibitor, acetaminophen, vicodin, oxycodone,ibuprofen, pethidine, dihydromorphine, codeine, cannabis, ketamine,duloxetine, and/or the like.

A “target region” refers to an area to receive treatment based on the NStherapy. For example, the target region may correspond to peripheralnerves, locations within a brain, appendages of the patient (e.g., legs,arms), one or more muscle groups, and/or the like. The target region maybe proximate to and/or remote from the neural tissue of interestreceiving the NS therapy. For example, the NS system can be positionedproximate to the spinal cord. The NS system delivers the NS therapy tothe neural tissue of interest proximate to the spinal cord. The NStherapy is configured to provide treatment to the target region, such asthe leg, arm, and/or the like distant and biologically coupled to theneural tissue of interest. Additionally or alternatively, the NS therapyis delivered to neural tissue of interest proximate to the targetregion. For example, the NS system may be positioned within the skullproximate to the brain. The NS system delivers the NS therapy to neuraltissue of interest corresponding to the target region.

A “drug retention device” refers to a container holding one or moredoses of the drug. The drug retention device may be a bottle, syringe, adrug tray, a blister package, a plastic bag, and/or the like.Optionally, the drug retention device may communicate to the NS system.For example, the drug retention device may include an RF circuitconfigured to communication with the NS system. For example, the RFcircuit may utilize a wireless communication standard such as radiofrequency identification (RFID), near field communication (NFC),Bluetooth and/or the like. The drug retention device may be configuredto transmit a message indicating the trigger event to the NS system whenthe drug retention device is opened.

FIG. 1 depicts a schematic block diagram of an embodiment of aneurostimulation (NS) system 100. The NS system 100 is configured togenerate electrical pulses (e.g., excitation pulses) for application toneural tissue of the patient according to one embodiment. For example,the NS system 100 may be adapted to stimulate spinal cord tissue, dorsalroot, dorsal root ganglion (DRG), peripheral nerve tissue, deep braintissue, cortical tissue, cardiac tissue, digestive tissue, pelvic floortissue, and/or any other suitable neural tissue of interest within abody of a patient.

The NS system 100 includes an implantable pulse generator (IPG) 150 thatis adapted to generate electrical pulses for application to tissue of apatient. The IPG 150 typically comprises a metallic housing or can 158that encloses a controller circuit 151, pulse generating circuitry 152,a charging coil 153, a battery 154, a communication circuit 155, batterycharging circuitry 156, switching circuitry 157, memory 161, and/or thelike. The communication circuit 155 may represent hardware that is usedto transmit and/or receive data along a uni-directional communicationlink and/or bi-directional communication link (e.g., with an externaldevice 160, a drug retention device).

The controller circuit 151 is configured to control the operation of theNS system 100. The controller circuit 151 may include one or moreprocessors, a central processing unit (CPU), one or moremicroprocessors, or any other electronic component capable of processinginput data according to program instructions. Optionally, the controllercircuit 151 may include and/or represent one or more hardware circuitsor circuitry that include, are connected with, or that both include andare connected with one or more processors, controllers, and/or otherhardware logic-based devices. Additionally or alternatively, thecontroller circuit 151 may execute instructions stored on a tangible andnon-transitory computer readable medium (e.g., the memory 161).

The IPG 150 may include a separate or an attached extension component170. The extension component 170 may be a separate component. Forexample, the extension component 170 may connect with a “header” portionof the IPG 150, as is known in the art. If the extension component 170is integrated with the IPG 150, internal electrical connections may bemade through respective conductive components. Within the IPG 150,electrical pulses are generated by the pulse generating circuitry 152and are provided to the switching circuitry 157. The switching circuitry157 connects to outputs of the IPG 150. Electrical connectors (e.g.,“Bal-Seal” connectors) within the connector portion 171 of the extensioncomponent 170 or within the IPG header may be employed to conductvarious stimulation pulses. The terminals of one or more leads 110 areinserted within the connector portion 171 or within the IPG header forelectrical connection with respective connectors. The pulses originatingfrom the IPG 150 are provided to the one or more leads 110. The pulsesare then conducted through the conductors of the lead 110 and applied totissue of a patient via an electrode array 111. Any suitable known orlater developed design may be employed for connector portion 171.

The electrode array 111 may be positioned on a paddle structure of thelead 110. For example, in a planar formation on a paddle structure asdisclosed in U.S. Provisional Application No. 61/791,288, entitled,“PADDLE LEADS FOR NEUROSTIMULATION AND METHOD OF DELIVERYING THE SAME,”which is expressly incorporated herein by reference. The electrode array111 includes a plurality of electrodes 112 aligned along correspondingrows and columns. Each of the electrodes 112 are separated bynon-conducting portions of the paddle structure, which electricallyisolate each electrode 112 from an adjacent electrode 112. Thenon-conducting portions may include one or more insulative materialsand/or biocompatible materials to allow the lead 110 to be implantablewithin the patient. Non-limiting examples of such materials includepolyimide, polyetheretherketone (PEEK), polyethylene terephthalate (PET)film (also known as polyester or Mylar), polytetrafluoroethylene (PTFE)(e.g., Teflon), or parylene coating, polyether bloc amides,polyurethane. The electrodes 112 may be configured to emit pulses in anoutward direction.

Optionally, the IPG 150 may have one or more leads 110 connected via theconnector portion 171 of the extension component 170 or within the IPGheader. For example, a DRG stimulator, a steerable percutaneous lead,and/or the like. Additionally or alternatively, the electrodes 112 ofeach lead 110 may be configured separately to emit excitation pulses.

FIGS. 2A-2I, respectively, depict stimulation portions 200-208 forinclusion at the distal end of the lead 110. For example, thestimulation portions 200-208 depict a conventional stimulation portionof a “percutaneous” lead with multiple electrodes 112. The stimulationportions 200-208 depict a stimulation portion including severalsegmented electrodes 112. Example fabrication processes are disclosed inU.S. patent application Ser. No. 12/895,096, entitled, “METHOD OFFABRICATING STIMULATION LEAD FOR APPLYING ELECTRICAL STIMULATION TOTISSUE OF A PATIENT,” which is incorporated herein by reference.Stimulation portions 204-208 include multiple electrodes 112 onalternative paddle structures than shown in FIG. 1.

In connection to FIG. 1, the lead 110 may include a lead body 172 ofinsulative material about a plurality of conductors within the materialthat extend from a proximal end of lead 110, proximate to the IPG 150,to its distal end. The conductors electrically couple a plurality of theelectrodes 112 to a plurality of terminals (not shown) of the lead 110.The terminals are adapted to receive electrical pulses and theelectrodes 112 are adapted to apply the pulses to the stimulation targetof the patient. It should be noted that although the lead 110 isdepicted with twenty electrodes 112, the lead 110 may include anysuitable number of electrodes 112 (e.g., less than twenty, more thantwenty) as well as terminals, and internal conductors.

Although not required for all embodiments, the lead body 172 of the lead110 may be fabricated to flex and elongate upon implantation oradvancing within the tissue (e.g., nervous tissue) of the patienttowards the stimulation target and movements of the patient during orafter implantation. By fabricating the lead body 172, according to someembodiments, the lead body 172 or a portion thereof is capable ofelastic elongation under relatively low stretching forces. Also, afterremoval of the stretching force, the lead body 172 may be capable ofresuming its original length and profile. For example, the lead body maystretch 10%, 20%, 25%, 35%, or even up or above to 50% at forces ofabout 0.5, 1.0, and/or 2.0 pounds of stretching force. Fabricationtechniques and material characteristics for “body compliant” leads aredisclosed in greater detail in U.S. Provisional Patent Application No.60/788,518, entitled “Lead Body Manufacturing,” which is expresslyincorporated herein by reference.

For implementation of the components within the IPG 150, a processor andassociated charge control circuitry for an IPG is described in U.S. Pat.No. 7,571,007, entitled “SYSTEMS AND METHODS FOR USE IN PULSEGENERATION,” which is expressly incorporated herein by reference.Circuitry for recharging a rechargeable battery (e.g., battery chargingcircuitry 156) of an IPG using inductive coupling and external chargingcircuits are described in U.S. Pat. No. 7,212,110, entitled “IMPLANTABLEDEVICE AND SYSTEM FOR WIRELESS COMMUNICATION,” which is expresslyincorporated herein by reference.

An example and discussion of “constant current” pulse generatingcircuitry (e.g., pulse generating circuitry 152) is provided in U.S.Patent Publication No. 2006/0170486 entitled “PULSE GENERATOR HAVING ANEFFICIENT FRACTIONAL VOLTAGE CONVERTER AND METHOD OF USE,” which isexpressly incorporated herein by reference. One or multiple sets of suchcircuitry may be provided within the IPG 150. Different pulses ondifferent electrodes 112 may be generated using a single set of thepulse generating circuitry 152 using consecutively generated pulsesaccording to a “multi-stimset program” as is known in the art. Complexstimulation parameters may be employed such as those described in U.S.Pat. No. 7,228,179, entitled “Method and apparatus for providing complextissue stimulation patterns,” and International Patent PublicationNumber WO 2001/093953 A1, entitled “NEUROMODULATION THERAPY SYSTEM,”which are expressly incorporated herein by reference. Alternatively,multiple sets of such circuitry may be employed to provide pulsepatterns (e.g., the tonic stimulation waveform, the burst stimulationwaveform) that include generated and delivered stimulation pulsesthrough various electrodes 112 of the one or more leads 110 as is alsoknown in the art. Various sets of stimulation parameters may define thecharacteristics and timing for the pulses applied to the variouselectrodes 112 as is known in the art. Although constant excitationpulse generating circuitry is contemplated for some embodiments, anyother suitable type of pulse generating circuitry may be employed suchas constant voltage pulse generating circuitry.

The external device 160 may be implemented to charge/recharge thebattery 154 of the IPG 150 (although a separate recharging device couldalternatively be employed), to access the memory 161, to program the IPG150 when implanted within the patient, to communicate triggering eventsto the NS system 100, and/or the like. FIG. 3 depicts a schematic blockdiagram of an embodiment of the external device 160. The external device160 may be a workstation, a portable computer, an NS system programmer,a PDA, a cell phone, a smart phone, a tablet, and/or the like.

The external device 160 includes an internal bus thatconnects/interfaces with a Central Processing Unit (CPU) 302, ROM 304,RAM 306, a hard drive 308, a speaker 310, a printer 312, a CD-ROM drive314, a floppy drive 316, a parallel I/O circuit 318, a serial I/Ocircuit 320, a display 322, a touch screen 324, a standard keyboardconnection 326, custom keys 328, and a radio frequency (RF) subsystem330. The internal bus is an address/data bus that transfers informationbetween the various components described herein. The hard drive 308 maystore operational programs as well as data, such as waveform templatesand detection thresholds.

The CPU 302 is configured to control the operation of the externaldevice 160. The CPU 302 may include one or more processors. Optionally,the CPU 302 may include one or more microprocessors, a graphicsprocessing unit (GPU), or any other electronic component capable ofprocessing inputted data according to specific logical instructions.Optionally, the CPU 302 may include and/or represent one or morehardware circuits or circuitry that include, are connected with, or thatboth include and are connected with one or more processors, controllers,and/or other hardware logic-based devices. Additionally oralternatively, the CPU 302 may execute instructions stored on a tangibleand non-transitory computer readable medium (e.g., the ROM 304, the RAM306, hard drive 308).

Optionally, the CPU 302 may include RAM or ROM memory, logic and timingcircuitry, state machine circuitry, and/or I/O circuitry to interfacewith the NS system 100. The display 322 may be connected to a videodisplay 332. The touch screen 324 may display graphic informationrelating to the NS system 100. The display 322 displays variousinformation related to the processes described herein.

The touch screen 324 accepts a user's touch input 334 when selectionsare made. The keyboard 326 (e.g., a typewriter keyboard 336) allows theuser to enter data to the displayed fields, as well as interface withthe RF subsystem 330. The touch screen 324 and/or the keyboard 326 isconfigured to allow the user to operate the NS system 100. The externaldevice 160 may be controlled by the user (e.g., doctor, clinician,patient) through the touch screen 324 and/or the keyboard 326 allowingthe user to interact with the NS system 100. The touch screen 324 and/orthe keyboard 326 may permit the user to move electrical stimulationalong and/or across one or more of the lead(s) 110 using differentelectrode 112 combinations, for example, as described in U.S. PatentApplication Publication No. 2009/0326608, entitled “METHOD OFELECTRICALLY STIMULATING TISSUE OF A PATIENT BY SHIFTING A LOCUS OFSTIMULATION AND SYSTEM EMPLOYING THE SAME,” which is expresslyincorporated herein by reference. Optionally, the touch screen 324and/or the keyboard 326 may permit the user to designate whichelectrodes 112 are to stimulate (e.g., emit excitation pulses, in ananode state, in a cathode state) the stimulation target.

Custom keys 328 turn on/off 338 the external device 160. The printer 312prints copies of reports 340 for a physician to review or to be placedin a patient file, and the speaker 310 provides an audible warning(e.g., sounds and tones 342) to the clinician and/or patient. Theparallel I/O circuit 318 interfaces with a parallel port 344. The serialI/O circuit 320 interfaces with a serial port 346. The floppy drive 316accepts diskettes 348. Optionally, the floppy drive 316 may include aUSB port or other interface capable of communicating with a USB devicesuch as a memory stick. The CD-ROM drive 314 accepts CD ROMs 350.

The RF subsystem 330 includes a central processing unit (CPU) 352 inelectrical communication with an RF circuit 354. The RF subsystem 330 isconfigured to receive and/or transmit information with the NS system100. The RF subsystem 330 may represent hardware that is used totransmit and/or receive data along a uni-directional and/orbi-directional communication link. The RF subsystem 330 may include atransceiver, receiver, transceiver and/or the like and associatedcircuitry (e.g., antennas) for wirelessly communicating (e.g.,transmitting and/or receiving) with the NS system 100. For example,protocol firmware for transmitting and/or receiving data along theuni-directional and/or bi-directional communication link may be storedin the memory (e.g., the ROM 304, the RAM 306, the hard drive 308),which is accessed by the CPU 352. The protocol firmware provides thenetwork protocol syntax for the CPU 352 to assemble data packets,establish and/or partition data received along the uni-directionaland/or bi-directional communication links, and/or the like. Theuni-directional and/or bi-directional communication link can represent awireless communication (e.g., utilizing radio frequency (RF)) link forexchanging data (e.g., data packets) between the NS system 100 and theexternal device 160. The uni-directional and/or bi-directionalcommunication link may be based on a customized communication protocoland/or a standard communication protocol, such as Bluetooth, NFC, RFID,GSM, infrared wireless LANs, HIPERLAN, 3G, LTE, and/or the like.

Additionally or alternatively, the RF subsystem 330 may be operablycoupled to a “wand” 165 (FIG. 1). The wand 165 may be electricallyconnected to a telemetry component 166 (e.g., inductor coil, RFtransceiver) at the distal end of wand 165 through respective wires (notshown) allowing bi-directional communication with the NS system 100. Forexample, the user may initiate communication with the NS system 100 byplacing the wand 165 proximate to the NS system 100. Preferably, theplacement of the wand 165 allows the telemetry system of the wand 165 tobe aligned with the communication circuit 155.

Also, the external device 160 may permit operation of the IPG 150according to one or more NS programs or therapies to treat the patient.For example, the NS program corresponds to the NS therapy and/orexecuted by the IPG 150. Each NS program may include one or more sets ofstimulation parameters of the pulses including pulse amplitude,stimulation level, pulse width, pulse frequency or inter-pulse period,pulse repetition parameter (e.g., number of times for a given pulse tobe repeated for respective stimset during execution of program),biphasic pulses, monophasic pulses, etc. The IPG 150 may modify itsinternal parameters in response to the control signals from the externaldevice 160 to vary the stimulation characteristics of the stimulationpulses transmitted through the lead 110 to the tissue of the patient. NSsystems, stimsets, and multi-stimset programs are discussed in PCTPublication No. WO 01/93953, entitled “NEUROMODULATION THERAPY SYSTEM,”and U.S. Pat. No. 7,228,179, entitled “METHOD AND APPARATUS FORPROVIDING COMPLEX TISSUE STIMULATION PATTERNS,” which are expresslyincorporated herein by reference.

FIG. 4 illustrates a flowchart of an embodiment of a method 400 foradjusting a NS therapy. The method 400, for example, may employstructures or aspects of various embodiments (e.g., systems and/ormethods) discussed herein. In various embodiments, certain steps (oroperations) may be omitted or added, certain steps may be combined,certain steps may be performed simultaneously, certain steps may beperformed concurrently, certain steps may be split into multiple steps,certain steps may be performed in a different order, or certain steps orseries of steps may be re-performed in an iterative fashion. In variousembodiments, portions, aspects, and/or variations of the method 400 maybe used as one or more algorithms to direct hardware to perform one ormore operations described herein.

Beginning at 402, the CPU 302 calculates an absorption curve 502 of adrug over time. FIG. 5 illustrates a graphical representation 500 of anembodiment of the absorption curve 502. The absorption curve 502 is arepresentation of a concentration of the drug in blood plasma, shownalong a vertical axis 506, of the patient over time, shown along ahorizontal axis 504. The absorption curve 502 is based on apharmacokinetic characteristics of the drug. The pharmacokineticcharacteristics defines a model of a rate of concentration in the bloodplasma over time. The model is based on a rate of dissolution (e.g.,liberation) of the drug in the patient, a rate of movement of the drugin the bloodstream (e.g., absorption), and a rate of distribution of thedrug in the fluids and/or tissue of the patient from a location ofadministration of the drug. The pharmacokinetic characteristics may bestored in the memory (e.g., ROM 304, RAM 306, hard drive 308) of theexternal device 160. Additionally or alternatively, the pharmacokineticcharacteristics may be received by the external device 160 along auni-directional and/or bi-directional communication link established bythe RF subsystem 330. For example, the external device 160 may receivethe pharmacokinetic characteristics from a remote server provided by amanufacturer of the drug, regulatory agency, hospital, clinic, and/orthe like.

The pharmacokinetic characteristics can be different based on how thepatient receives the drug (e.g., how the drug is administered, a dosageof the drug). Based on the delivery method, the CPU 302 may select aportion of the pharmacokinetic characteristics and/or adjust thepharmacokinetic characteristics. The CPU 302 can determine how thepatient receives the drug based on selections by the clinician. Forexample, the clinician may use the touch screen 324 and/or the keyboard326 to enter details for the method of how the patient receives the drugand/or dosage. Based on the selections by the clinician, the CPU 302 mayselect and/or adjust the absorption curve 502. For example, if the drugis administered by a syringe, an initial slope 508 of the absorptioncurve 502 may be shifted earlier in time and/or increased from theexample in FIG. 5.

At 404, the CPU 302 determines a response curve 602 of a patient basedon a patient profile. FIG. 6 illustrates a graphical representation 600of an embodiment of the response curve 602. The response curve 602 is arepresentation of a physiological response of the patient, shown along avertical axis 606, based on a concentration of the drug, shown along ahorizontal axis 604. The physiological response of the patient isassociated with changes to one or more physiological characteristics ofthe patient. For example, the physiological response may include aninterruption and/or adjustment to the impulses produced or received byneural tissue within the patient.

The response curve 602 is affected by the patient profile. For example,the patient profile adjusts a response slope 608 of the response curve602. The patient profile includes physiological characteristics of thepatient. The physiological characteristics include a weight, an age, aheight, and/or the like of the patient. The physiologicalcharacteristics affect how the drug is absorbed by the patient, ametabolism of the drug by the patient, and/or the like.

The patient profile may be stored in the memory (e.g., ROM 304, RAM 306,hard drive 308) of the external device 160. Additionally oralternatively, the patient profile may be defined by the clinician. Forexample, the CPU 302 may receive the patient profile based on selectionsby the clinician received from the touch screen 324 and/or keyboard 326.Optionally, the patient profile may be received along a uni-directionaland/or bi-directional communication link from a remote server managed bya hospital, a clinic, and/or the like.

At 406, the CPU 302 calculates a drug efficacy model 700 based on theabsorption curve 502 and the response curve 602. FIG. 7 illustrates agraphical representation of an embodiment of the drug efficacy model700. The drug efficacy model 700 is shown as a waveform 702. Thewaveform 702 represents a magnitude of physiological effects of the drugon the patient, shown along a vertical axis 706, over time, shown alonga horizontal axis 704. The drug efficacy model 700 is derived by the CPU302 from the absorption curve 502 and the response curve 602. Forexample, the CPU 302 calculates the drug efficacy model 700 based on aconvolution between the absorption curve 502 and the response curve 602.The waveform 702 includes a drug efficacy that begins at a point 708,representing the trigger event. The waveform 702 includes a peak 709.The peak 709 represents a point or range in time when the physiologicaleffects of the drug on the patient is at a peak and/or maximumphysiological effect. Over time, the waveform 702 is reduced overtime,based on a reduction in concentration of the drug until reaching aminimal point 710. The minimal point 710 represents when the point atwhich the physiological effects of the drug on the patient is negligibleand/or not present within the patient.

At 408, the CPU 302 defines a PS profile based on the drug efficacymodel 700. Optionally, the PS profile includes the drug efficacy model700 that is based on the absorption curve 502 of the drug over time, apharmacokinetic characteristic of the drug, and/or the response curve602 of the patient. Additionally or alternatively, the PS profileincludes an NS therapy profile over time in which a stimulationintensity is reduced as the drug efficacy increases. The PS profileincludes values for the stimulation parameters of the NS therapy overtime based on the trigger event (e.g., at the point 708). The PS profilemay adjust the stimulation parameters of the NS therapy in connectionwith changes in a magnitude of the physiological effect of the drug. Theadjustment to the stimulation parameters over time represent the NStherapy profile.

FIGS. 8-11 illustrate graphical representations of embodiments of PSprofiles 800, 900, 1000, 1100. The PS profiles 800, 900, 1000, 1100extend from corresponding trigger event until, through peak drugeffectiveness, to a point the physiological effects of the drug arenegligible and/or no longer present in the patient. The PS profiles 800,900, 1000, 1100 are shown temporally aligned with the drug efficacymodel 700. For example, the PS profiles 800, 900, 1000, 1100 are alignedwith the trigger event at the point 708 of the waveform 702. The PSprofiles 800, 900, 1000, 1100 include sets of stimulation parameters orweighting factors over time for the NS therapy. The sets of stimulationparameters or weighted factors that change over time. The PS profiles800, 900, 1000, 1100 are configured to reduce a stimulation intensity ofthe NS therapy as the drug efficacy increases, and increases thestimulation intensity as the drug efficacy decreases. For example, thePS profiles 800, 900, 1000, 1100 are configured to have minimumstimulation parameters at the peak 709 of the waveform 702 and maximumstimulation parameters at the valleys of the drug efficacy model 700.

FIG. 8 illustrates an NS therapy waveform 802 that represents the NStherapy profile for the NS therapy. The NS therapy waveform 802 extendsalong a horizontal axis 801 representing time, and a vertical axis 805representing a weighted factor. The NS therapy waveform 802 extends froma maximum stimulation parameters 804 to a minimum stimulation parameters808 and returning to a maximum stimulation parameters 806. The maximumstimulation parameters 804, 806 may correspond to the stimulationparameters for the NS therapy when the drug is not administered to thepatient. For example, the maximum stimulation parameters 804, 806 areassociated when the physiological effects of the drug are negligibleand/or not present within the patient. The minimum stimulation parameter808 may correspond to when the physiological effects of the drug are atthe peak 709. The maximum and minimum stimulation parameters 804, 806,808 can be stored in the memory (e.g., the ROM 304, the RAM 306, thehard drive 308). Optionally, the maximum and minimum stimulationparameters 804, 806, 808 may be defined by the clinician. For example,the CPU 302 may receive the maximum and minimum stimulation parameters804, 806, 808 from the touch screen 324 and/or keyboard 326.

The NS therapy waveform 802 may represent weighted factors that varyover time defining the NS therapy profile. The NS therapy waveform 802is defined as a range of stimulation parameters from the maximumstimulation parameters 804, 806 and the minimum stimulation parameter808. The weighted factors of the NS therapy waveform 802 shift thevalues for the stimulation parameters along the range based on anelapsed time. For example, the weighted factors may represent apercentage and/or portion of the maximum stimulation parameters 804,806. The portion of the maximum stimulation parameters 804, 806 may befor one or more of the stimulation parameters of the NS therapy. Forexample, the weighted factors may be for at least one of the pulsewidth, the frequency, the amplitude, the duty cycle, and/or the like ofthe NS therapy. The different weighted factors can represent differentstimulation intensities of the stimulation parameters.

Additionally or alternatively, the weighted factors may adjust the NStherapy type. For example, the maximum stimulation parameters 804, 806may correspond to the burst stimulation waveform. The weighted factorsmay represent a number of pulses of the burst stimulation waveform. Theweighted factors continually reduce a number of pulses grouped to formthe pulse train of the burst stimulation waveform reaching the minimumstimulation parameter 808. For example, the minimum stimulationparameter 808 may represent a tonic stimulation waveform having a singlepulse.

The NS therapy waveform 802 may be defined by the CPU 302 based on thedrug efficacy model 700. For example, the NS therapy waveform 802 mayrepresent an inverse of the waveform 702. The CPU 302 may normalize theinverse of the waveform 702 to form the NS therapy waveform 802. Forexample, the CPU 302 may adjust opposing ends and minimum of the inverseof the NS therapy waveform 802 to match the maximum and minimumstimulation parameters 804, 806, 808.

FIG. 9 illustrates a set of stimulation parameters 910-912 thatrepresents the NS therapy profile of different stimulation parameters ofthe NS therapy. For example, the set of stimulation parameters 910-912can have at least one different stimulation parameter such as the pulsewidth, the frequency, the amplitude, the duty cycle, the NS therapytype, and/or the like with respect to each other. The set of stimulationparameters 910-912 may correspond to different stimulation intensitiesof the NS therapy, which are plotted along a vertical axis 914. Thevertical axis 914 representing the stimulation intensity. For example,the set of stimulation parameters 910 have a larger stimulationintensity than the set of stimulation parameters 911-912. In anotherexample, the set of stimulation parameters 911 have a larger stimulationintensity than the set of stimulation parameters 912. The difference inthe stimulation intensity can be based on a magnitude of the pulsewidth, the frequency, the amplitude, the duty cycle, and/or the likerelative to the remaining sets of stimulation parameters 910-912.

The set of stimulation parameters 910-912 occur over a duration of time.The duration of the set of stimulation parameters 910-912 is based onthe drug efficacy model 700. For example, the duration of the set ofstimulation parameters 910-912 may be based on the magnitude ofphysiological effects (e.g., along the vertical axis 706) shown from thedrug efficacy model 700. The magnitude of physiological effects maydefine thresholds 902-905. The magnitudes may correspond to differentthreshold 902-905. The thresholds 902-905 may define the duration of theset of stimulation parameters 910-912. For example, from the triggerevent to the patient to the threshold 902 may define the duration of theset of stimulation parameters 910. The set of stimulation parameters 910may correspond to a maximum stimulation parameter. For example, the setof stimulation parameters 910 may be similar to and/or the same as themaximum stimulation parameters 804, 806.

Between the thresholds 902 and 903 and the thresholds 904 and 905,define the duration for the set of stimulation parameters 911. Thethresholds 903 and 904 define the duration for the set of stimulationparameters 912. The set of stimulation parameters 912 represent aminimum stimulation parameters of the PS profile 900. The set ofstimulation parameters 912 is configured by the CPU 302 to occur duringthe peak 709 of the drug efficacy model 700. The set of stimulationparameters 912 may correspond to a minimum stimulation parameters. Forexample, the set of stimulation parameters 912 may be similar to and/orthe same as the minimum stimulation parameters 808. The threshold 905 tothe minimal point at 710 may define the set of stimulation parameters910.

Additionally or alternatively, the PS profile may include more thanthree set of stimulation parameters 910-912 and/or less than three setof stimulation parameters.

FIG. 10 illustrates a set of stimulation parameters 1005-1006 thatrepresents the NS therapy profile for the NS therapy. The set ofstimulation parameters 1005-1006 may represent different stimulationparameters of the NS therapy. For example, the set of stimulationparameters 1005-1006 can have at least one different stimulationparameter such as the pulse width, the frequency, the amplitude, theduty cycle, the NS therapy type, and/or the like with respect to eachother. The set of stimulation parameters 1005-1006 may correspond todifferent stimulation intensities of the NS therapy. The set ofstimulation parameters 1005 may correspond to a maximum stimulationparameter. For example, the set of stimulation parameters 1005 may besimilar to and/or the same as the maximum stimulation parameters 804,806. The set of stimulation parameters 1006 may correspond to a minimumstimulation parameters. For example, the set of stimulation parameters1006 may be similar to and/or the same as the minimum stimulationparameters 808.

The set of stimulation parameters 1005-1006 occur over a duration andvary over time. Similar to and/or the same as the set of stimulationparameters 910-912, the set of stimulation parameters 1005-1006 is basedon the drug efficacy model 700. For example, the duration of the set ofstimulation parameters 1005-1006 may be based on the magnitude ofphysiological effects defining thresholds 1002-1003. The thresholds1002-1003 may define the duration of the set of stimulation parameters1005-1006. For example, when the drug is administered to the patient tothe threshold 1002 may define the duration of the set of stimulationparameters 1005. Between the thresholds 1002 and 1003, define theduration for the set of stimulation parameters 1006. The set ofstimulation parameters 1006 having lower stimulation intensity relativeto the set of stimulation parameters 1005 is configured to occur duringthe peak 709. The threshold 1006 to the minimal point at 710 may definethe set of stimulation parameters 1005.

The sets of stimulation parameters 910-912, 1005-1006 can be stored inthe memory (e.g., the ROM 304, the RAM 306, the hard drive 308).Optionally, sets of stimulation parameters 910-912, 1005-1006 may bedefined by the clinician. For example, the CPU 302 may receive the setsof stimulation parameters 910-912, 1005-1006 from the touch screen 324and/or keyboard 326.

FIG. 11 illustrates weighted factors 1105-1109 that represents the NStherapy profile for the NS therapy. The weighted factors 1105-1109 shiftvalues of the stimulation parameters of the NS therapy along a range1102 based on an elapsed time. The weighted factors 1105-1109 correspondto different stimulation intensities plotted along a vertical axis 1110.The weighted factors 1105-1109 are positioned at different points withinthe range 1102 and in time. The positions of the weighted factors1105-1009 are based on the magnitude of the physiological effect of thedrug efficacy model 700. For example, the weighted factors 1105-1109 areconfigured such that a minimum stimulation intensity occurs during thepeak 709. The weighted factors 1105-1109 adjust at least one differentstimulation parameter, such as the pulse width, the frequency, theamplitude, the duty cycle, the NS therapy type, and/or the like of theNS therapy relative to a maximum stimulation parameters 1112. Forexample, the weighted factors 1105-1109 may represent a percentage of amaximum stimulation parameters 1112. The weighted factors 1105-1109 maycorrespond to a reduction of the maximum stimulation parameters 1112.For example, the weighted factors 1105-1109 may be associated with aportion of the maximum stimulation parameters 1112.

At 410, the CPU 302 determines whether adjustments are received to thePS profile 800, 900, 1000, 1100. For example, the CPU 302 may determinebased on selections by the clinician from the touchscreen 324 or thekeyboard 326 to adjust the PS profile 800, 900, 1000, 1100.

If the CPU 302 determined that adjustments were received, then at 412,the CPU 302 adjusts the PS profile 800, 900, 1000, 1100 based on thereceived clinician inputs. Optionally, the adjustments to the PS profile800, 900, 1000, 1100 adjust the stimulation intensity of the NS therapyprofile. For example, the clinician may administer the drug to thepatient. The clinician may adjust the maximum stimulation parameters804, 806, 1112, the sets of stimulation parameters 910-912, 1005-1006,and/or the weight factors 1105-1109 based on patient feedback. If thepatient feels pain from the NS therapy after the drug is administered,the clinician may reduce the maximum stimulation parameters 804, 806,1112, the sets of stimulation parameters 910, 1005, and/or the weightfactors 1105. If the patient feels pain during the peak 709 of the drugefficacy model 700, the clinician may decrease the minimum stimulationparameters 808, the sets of stimulation parameters 912, 1006, and/or theweight factors 1109.

At 414, the external device 160 transmits the PS profile 800, 900, 1000,1100 to the NS system 100. For example, the CPU 302 instructs the RFsubsystem 330 to transmit the PS profile 800, 900, 1000, 1100 along auni-directional and/or bi-directional communication link. Additionallyor alternatively, the CPU 302 may instruct the RF subsystem 330 totransmit the PS profile 800, 900, 1000, 1100 based on selections by theclinician. For example, the clinician may instruct the CPU 302 totransmit the PS profile 800, 900, 1000, 1100 based on a selection fromthe touch screen 324 and/or the keyboard 326. When the PS profile 800,900, 1000, 1100 is received by the NS system 100, the controller circuit151 (FIG. 1) stores the PS profile 800, 900, 1000, 1100 in the memory161.

At 416, the controller circuit 151 instructs the IPG 150 to deliver theNS therapy to a portion of the electrodes 112 proximate to neural tissueof interest that is associated with the target region. The portion ofthe electrodes 112 may be selected when the NS system 100 is implantedwithin the patient. For example, the portion of the electrodes 112 fromthe electrode array 111 can be selected by the clinician when programmedby the external device 160. The portion of the electrodes 112 areselected by the clinician to deliver the NS therapy to the neural tissueof interest.

At 418, the controller circuit 151 determines if the trigger event isreceived. The trigger event is indicative of the drug being administeredto the patient. The trigger event can be received from the externaldevice 160. For example, the external device 160 may be managed by theclinician and/or the patient. When the drug is being administered to thepatient (e.g., orally, syringe, suppository), the CPU 302 receives aselection from the clinician and/or the patient from the touch screen324 and/or keyboard 326 to represent the trigger event. Based on theselection, the CPU 302 instructs the RF subsystem 330 to transmit thetrigger event along the uni-directional and/or bi-directionalcommunication link to the NS system 100.

Additionally or alternatively, the trigger event may be based on a drugschedule stored in the memory 161. For example, the PS profile 800, 900,1000, 1100 may include temporal information representing the drugschedule. The temporal information may represent times during the day,week, month, year, and/or the like when the drug is administered to thepatient. The controller circuit 151 may compare the temporal informationto a system clock. When the temporal information matches the systemclock, the controller circuit 151 determines that the trigger event isreceived.

Additionally or alternatively, the trigger event is received by thecontroller circuit 151 from the drug retention device. The drugretention device is configured to house one or more doses of the drug.The opening of the drug retention device is indicative of the patientbeing administered the drug. The drug retention device can include an RFcircuit. The RF circuit may be configured to transmit the trigger eventto the NS system 100 when the drug retention device is opened. Thetrigger event can be communicated to the NS system 100 via auni-directional and/or bi-directional communication link. When thetrigger event is received by the NS system 100, the controller circuit151 determines that the trigger event is received.

At 420, the controller circuit 151 instructs the IPG 150 to adjust theone or more of the stimulation parameters based on the PS profile 800,900, 1000, 1100. The adjustment of the one or more of the stimulationparameters is based on the trigger event. For example, the trigger eventrepresenting a start of the PS profile 800, 900, 1000, 1100.

In connection with FIG. 8, the controller circuit 151 instructs the IPG150 to adjust the one or more of the stimulation parameterscorresponding to the weighting factors of the PS profile 800. Forexample, the controller circuit 151 may traverse along the NS therapywaveform 802 representing the NS therapy profile. The NS therapywaveform 802 defining weighting factors to shift values of the one ormore of the stimulation parameters along the range. The range definedbetween the maximum stimulation parameter 804, 806 and the minimumstimulation parameter 808 of the NS therapy waveform 802. The controllercircuit 151 applies the weighting factors to shift the one or more ofthe stimulation parameters. For example, the controller circuit 151adjusts the one or more of the stimulation parameters based on theweighting factors with respect to the maximum stimulation parameters804, 806 over time relative to the trigger event.

In connection with FIG. 9, the controller circuit 151 instructs the IPG150 to adjust the one or more of the stimulation parameterscorresponding to the weighting factors of the PS profile 900. Forexample, the controller circuit 151 adjusts the one or more of thestimulation parameters correspond to the sets of the stimulationparameters 910-912. The controller circuit 151 adjusts the one or moreof the stimulation parameters to the set of the stimulation parameters910-912 based on durations defined by the thresholds 902-905. Forexample, the controller circuit 151 adjusts the one or more of thestimulation parameters from the set of the stimulation parameters 910 tothe set of the stimulation parameters 911 after the duration defined bythe threshold 902.

In connection with FIG. 11, the controller circuit 151 instructs the IPG150 to adjust the one or more of the stimulation parameterscorresponding to the weighting factors of the PS profile 1100. Forexample, the controller circuit 151 adjusts the one or more of thestimulation parameters correspond to the sets of the weighted factors1105-1109 representing the NS therapy profile. The controller circuit151 applies the weighted factors 1105-1109 to shift values of the one ormore stimulation parameters along the range 1102. For example, thecontroller circuit 151 adjusts the one or more of the stimulationparameters based on the weighted factors 1105-1109 over time relative tothe trigger event.

It may be noted that the various embodiments may be implemented inhardware, software or a combination thereof. The various embodimentsand/or components, for example, the modules, or components andcontrollers therein, also may be implemented as part of one or morecomputers or processors. The computer or processor may include acomputing device, an input device, a display unit and an interface, forexample, for accessing the Internet. The computer or processor mayinclude a microprocessor. The microprocessor may be connected to acommunication bus. The computer or processor may also include a memory.The memory may include Random Access Memory (RAM) and Read Only Memory(ROM). The computer or processor further may include a storage device,which may be a hard disk drive or a removable storage drive such as asolid-state drive, optical disk drive, and the like. The storage devicemay also be other similar means for loading computer programs or otherinstructions into the computer or processor.

As used herein, the term “computer,” “subsystem,” “controller circuit,”“circuit,” or “module” may include any processor-based ormicroprocessor-based system including systems using microcontrollers,reduced instruction set computers (RISC), ASICs, logic circuits, and anyother circuit or processor capable of executing the functions describedherein. The above examples are exemplary only, and are thus not intendedto limit in any way the definition and/or meaning of the term“controller circuit”.

The computer, subsystem, controller circuit, circuit execute a set ofinstructions that are stored in one or more storage elements, in orderto process input data. The storage elements may also store data or otherinformation as desired or needed. The storage element may be in the formof an information source or a physical memory element within aprocessing machine.

The set of instructions may include various commands that instruct thecomputer, subsystem, controller circuit, and/or circuit to performspecific operations such as the methods and processes of the variousembodiments. The set of instructions may be in the form of a softwareprogram. The software may be in various forms such as system software orapplication software and which may be embodied as a tangible andnon-transitory computer readable medium. Further, the software may be inthe form of a collection of separate programs or modules, a programmodule within a larger program or a portion of a program module. Thesoftware also may include modular programming in the form ofobject-oriented programming. The processing of input data by theprocessing machine may be in response to operator commands, or inresponse to results of previous processing, or in response to a requestmade by another processing machine.

As used herein, the terms “software” and “firmware” are interchangeable,and include any computer program stored in memory for execution by acomputer, including RAM memory, ROM memory, EPROM memory, EEPROM memory,and non-volatile RAM (NVRAM) memory. The above memory types areexemplary only, and are thus not limiting as to the types of memoryusable for storage of a computer program.

It is to be understood that the above description is intended to beillustrative, and not restrictive. For example, the above-describedembodiments (and/or aspects thereof) may be used in combination witheach other. In addition, many modifications may be made to adapt aparticular situation or material to the teachings of the inventionwithout departing from its scope. While the dimensions, types ofmaterials and coatings described herein are intended to define theparameters of the invention, they are by no means limiting and areexemplary embodiments. Many other embodiments will be apparent to thoseof skill in the art upon reviewing the above description. The scope ofthe invention should, therefore, be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Moreover, in the following claims, theterms “first,” “second,” and “third,” etc. are used merely as labels,and are not intended to impose numerical requirements on their objects.Further, the limitations of the following claims are not written inmeans—plus-function format and are not intended to be interpreted basedon 35 U.S.C. § 112(f), unless and until such claim limitations expresslyuse the phrase “means for” followed by a statement of function void offurther structure.

What is claimed is:
 1. A method to adjust a neurostimulation (NS)therapy, comprising: delivering an NS therapy to a portion of electrodesof a lead positioned proximate to neural tissue of interest that isassociated with a target region, wherein the NS therapy is defined bystimulation parameters; determining a trigger event indicative of a drugbeing administered to a patient, the drug configured to affect at leastone of the neural tissue of interest or the target region; and adjustingone or more of the stimulation parameters based on the PS profile. 2.The method of claim 1, wherein the PS profile includes a drug efficacymodel that is based on an absorption curve of the drug over time, apharmacokinetic characteristic of the drug; and a response curve of apatient.
 3. The method of claim 1, wherein the PS profile includes an NStherapy profile over time in which a stimulation intensity is reduced asa drug efficacy increases.
 4. The method of claim 3, wherein the NStherapy profile reduces the one or more stimulation parameters over timeto reduce the stimulation intensity.
 5. The method of claim 3, whereinthe NS therapy profile includes first and second sets of the stimulationparameters, and further comprising selecting between the first andsecond sets of the stimulation parameters based on an elapsed timerelative to the trigger event.
 6. The method of claim 5, furthercomprising receiving the first and second sets of the stimulationparameters from the external device.
 7. The method of claim 3, whereinthe NS therapy profile includes a range for the stimulation parameters,and further comprising applying a weighting factor to shift values forthe stimulation parameters along the range based on an elapsed timerelative to the trigger event.
 8. A method for adjusting aneurostimulation (NS) therapy, comprising: calculating an absorptioncurve of a drug over time, wherein the absorption curve is based on apharmacokinective characteristic of the drug; determining a responsecurve of a patient based on a patient profile, wherein the patientprofile represents one or more physiological characteristics of apatient; calculating a drug efficacy model based on the absorption curveand the response curve; defining a pharmacokinetic-stimulation (PS)profile based on the drug efficacy model; and transmitting the PSprofile to an NS system.
 9. The method of claim 8, wherein the PSprofile includes an NS therapy profile over time having a range ofstimulation parameters for an NS therapy, further comprising defining aweighting factor to shift values for the stimulation parameters alongthe range based on a morphology of the drug efficacy model.